Early, Consistent Glucose Control May Be Key to CVD Risk Reduction in Type 2 Diabetes: A Primary Care Analysis

Early, aggressive, and consistent control of hyperglycemia in the first year following a diagnosis of type 2 diabetes (T2D) was associated with a significant reduction in cardiovascular events of 25%, according to results of a new study from the University of Surrey in the United Kingdom.

The research team also found that greater glycemic variability during those first 12 months contributed to an increased risk for major adverse cardiovascular events (MACE) of approximately 21%. The findings were published online in Diabetes, Obesity and Metabolism.

"The conventional wisdom has been to slowly and steadily treat type 2 diabetes with diet and medicine dose-escalation over years - the period over which it took people to reduce their sugar levels after diagnosis was thought less important for major vascular protection. However, our observational study suggests that getting blood levels under control quickly – within the first 12 months after diagnosis – will significantly help reduce cardiovascular events,” said study investigator Martin Whyte, BSc, PhD, a reader in Metabolic Medicine at the University of Surrey, in a university statement.

Whyte and colleagues cite findings from the landmark UK Prospective Diabetes Study (UKPDS) that showed early tight glycemic control was associated with a reduction in macrovascular events, even if control subsequently deteriorated, the so-called “legacy” effect. Conversely, they note, aggressive control of hyperglycemia delayed for several years after onset of T2D may confer a negative prognosis for macrovascular events. The authors also highlight the few studies on and disagreement about the importance of glycemic variability either early in T2D treatment or after a period of glucose control.

To augment and potentially help clarify existing data, the researchers accessed a large primary care database of patients from across England to closely examine the impact on CVD of tight glycemic control and of variability in HbA1c during the first 12 months after T2D diagnosis.

For the retrospective cohort analysis, investigators identified adults with T2D in the Royal College of General Practitioners Research and Surveillance Centre database, which holds primary care records from for 1 595 170 individuals registered with 164 general medical practices in England.

For study inclusion the investigators required that individuals have a new diagnosis of T2D on or after January 1, 2005, be aged ≥25 years at the time of diagnosis, and have HbA1c measurements at both diagnosis and 1 year later as well as 5 or more measurements thereafter.

The authors created an indicator variable for glycemic change during the year after diagnosis by creating bands based on initial HbA1c level. The scheme led to 3 categories: Group A HbA1c 7.5%; group B, HbA1c 7.5%-9%; and group C HbA1c ≥ 9%. Whyte et al also used a glycemic variability score applied to HbA1c measures after the first 12 months to distinguish the effect of early glucose normalization from later glucose variability.

Investigators analyzed movement between HbA1c bands from time of diagnosis to 1 year and determined the association between specific shifts and risk for major adverse cardiovascular events (MACE) at 1-year post diagnosis. Time-varying Cox proportional hazards models were applied that included first-year transition and glycemic variability score.

The final cohort numbered 26 180 individuals with T2D of which 43.9% were women and 71% were white. At the time of data extraction, mean age was 68.7±12.6 years. For approximately half the cohort, diabetes duration was between 4 and 9 years. Mean body mass index (BMI) was 30.7±6.4 kg/m2 and blood pressure 139/81 mmHg. Median follow-up time was 1583 (IQR, 987-1737) days.

Looking specifically at shifts among glycemic bands from diagnosis to 1 year, 48% of individuals began in band A and maintained that status, 16.1% improved from band C to band A, and 14.6% improved from band B to band A.

Prior to a diagnosis of T2D, the authors report, there were 4179 MACE recorded among the 26 180 study patients followed by an additional 1457 events during the first 12 months after diagnosis. From the 1-year mark forward there were 2300 MACE.

When Whyte and colleagues modelled the effect of change from baseline HbA1c to 12-month value on CV outcome they found that, compared to those who maintained band A status from baseline to 1-year, those who transitioned from band C to band A during that time had a 25% reduced risk of MACE (HR, 0.75; 95% CI, 0.60-0.94; P=.014).

Conversely, those whose HbA1c did not improve from original band C status experienced an increase in risk of major adverse cardiovascular events (HR, 1.21; 95% CI, 0.81-1.81; P=.34).

Similarly, when researchers evaluated glycemic variability scores after the initial 12 months of HbA1c measures, they found the greatest level of variability conferred a higher risk of MACE (HR, 1.51; 95% CI, 1.11-2.06; P=.0096). They write that these data do support the concept of a legacy effect of early glucose control, “but with subsequent glycaemic variability contributing to an individual's risk profile.”

Of significant concern when looking at trends within groups, the authors say, is that younger adults, aged 25-44 years, were more likely to remain in band C during the year after diagnosis. As these are patients who may be more likely to reap a benefit from a legacy effect, the current finding should be explored further.

In conclusion the investigators reiterate that achieving an HbA1c <7.5% within 12 months of a T2D diagnosis and subsequently maintaining low glycemic variability lower risk for major macrovascular events. “Our findings support the concept that effort must be made to achieve rapid metabolic normalization after the diagnosis of diabetes in those with a low propensity to hypoglycemia,” they write.

Reference: Whyte MB, Joy M, Hinton W, et al. Early and ongoing stable glycaemic control is associated wtih a reduction in major adverse cardiovascular events in people with type 2 diabetes: A primary care cohort study. Diabetes Obes Metab. 2022 Apr 4. doi: 10.1111/dom.14705. Online ahead of print.